Induction of TSC-22 by treatment with a new anti-cancer drug, vesnarinone, in a human salivary gland cancer cell.
We undertook the present study to clarify the molecular mechanism of the effect of a new anti-cancer drug, vesnarinone, on a human salivary gland cancer cell line, TYS. We isolated TSC-22cDNA as avesnarinone-inducible gene from a cDNA library constructed from vesnarinone-treated TYS cells. TSC-22 was originally reported as a transforming growth factor (TGF)-beta-inducible gene. The expression of TSC-22 was up-regulated within a few hours after treatment with vesnarinone and was continued for 3 days. The level of TSC-22 mRNA in TYS cells was continuously increased until the cells reached confluency. Furthermore, the induction of TSC-22 by vesnarinone was inhibited by treatment with cycloheximide. When we treated the cells with an antisense oligonucleotide against TSC-22 mRNA under quiescent conditions, the antisense oligonucleotide stimulated the growth of TYS cells; however, under growing conditions the antisense oligonucleotide did not affect cell growth. Furthermore, the antisense oligonucleotide suppressed the antiproliferative effect of vesnarinone. These results suggest that TSC-22 may be a negative growth regulator and may play an important role in the antiproliferative effect of vesnarinone.
Kawamata
H
H
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Kuramoto, Japan.
Nakashiro
K
K
Uchida
D
D
Hino
S
S
Omotehara
F
F
Yoshida
H
H
Sato
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D012097:Repressor Proteins; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D011719:Pyrazines; D011804:Quinolines; D012333:RNA, Messenger; D012097:Repressor Proteins; C099726:TSC22D1 protein, human; D014157:Transcription Factors; C041667:vesnarinone